A microemulsion type rhinitis liquid cotton swab and a preparation method thereof

Abstract

The application discloses a microemulsion type rhinitis liquid cotton swab and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The cotton swab comprises a cotton rod and a medical absorbent cotton head coated on the end of the cotton rod, and the cotton rod is filled with the microemulsion type rhinitis liquid. The microemulsion type rhinitis liquid is composed of an oil phase, an aqueous phase, an emulsifier, a preservative antibacterial agent and a traditional Chinese medicine extract powder. The oil phase comprises xanthium oil, baizhi oil, thinleaf galangal oil, fangfeng oil, licorice oil, marigold oil, huangqi oil, fuyunye oil, xinyi oil and menthol. The emulsifier is polyoxyethylene 40 hydrogenated castor oil, and the mass ratio of the oil phase to the emulsifier is 1:5. The microemulsion type rhinitis liquid is a clear and transparent oil-in-water microemulsion, has good stability and no irritation, is filled in a disposable breakable cotton swab, is convenient, safe and sanitary to use, has rapid effect, long-acting effect and can effectively relieve the symptoms of nasal congestion and nasal dryness, and has a good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a microemulsion nasal solution cotton swab for relieving symptoms of rhinitis and nasal congestion, and its preparation method. Background Technology

[0002] Rhinitis is an inflammatory reaction of the nasal mucosa. Clinically, it often manifests as symptoms such as nasal congestion, runny nose, sneezing, and nasal itching. The symptoms are characterized by seasonal onset or irregular onset throughout the year. The course of the disease often lasts for more than several months and recurs frequently, seriously affecting the patient's breathing comfort, sleep quality, and overall life experience.

[0003] Currently, medications for nasal congestion caused by rhinitis mainly include antihistamines and nasal corticosteroids. While the combination of these two can quickly relieve nasal congestion, the duration of use must be strictly controlled, as long-term use can easily cause adverse reactions such as nasal dryness, nosebleeds, and local irritation. In terms of dosage forms, clinically used rhinitis medications mainly include nasal sprays, nasal drops, nasal irrigators, oral tablets / capsules, hot melt adhesive patches, and hydrogel patches. However, all of the above dosage forms have varying degrees of defects in practical applications: sprays easily irritate the nasal mucosa, causing a sneezing reflex, which leads to the expulsion of the medication and affects its efficacy; nasal drops are prone to backflow into the throat, and some drops containing volatile oils also have a noticeable greasy feel, resulting in poor patient compliance; nasal irrigators are complicated to use and easily cause choking; oral preparations have a slow onset of action, exhibit a first-pass effect in the liver, have low bioavailability, and are inconvenient for patients who have difficulty swallowing; hot melt adhesive patches have a low transdermal drug release rate, require high-temperature heating during preparation, which easily leads to the decomposition and inactivation of active ingredients such as volatile oils and alkaloids in traditional Chinese medicine, and long-term application can easily cause hair follicle blockage and skin allergies; hydrogel patches have poor breathability, easily cause skin maceration, and have weak adhesion, making them easy to fall off.

[0004] In recent years, nasal spray swabs with natural Chinese herbal extracts as their core ingredient have gradually gained attention due to their advantages such as ease of use, wide range of applications, high safety, good hygiene, and rapid relief of nasal congestion. For example, there are existing reports of products that make volatile oils or extracts of Chinese herbs into liquid and then fill them into cotton swabs. Before use, the cotton swab is gently broken, and the liquid in the tube flows out to the cotton tip, which is then applied to the nasal cavity and acts directly on the nasal mucosa.

[0005] In the field of microemulsion formulations, microemulsions are thermodynamically stable systems composed of an oil phase, an aqueous phase, an emulsifier, and a co-emulsifier. They are characterized by small particle size (generally 10-100 nm), uniform distribution, good light transmittance, and the ability to remain intact for extended periods without stratification, thus improving the solubility and bioavailability of poorly soluble drugs. Existing research has applied microemulsion technology to the formulation development of traditional Chinese medicine extracts. For example, Chinese patent CN105998286A discloses a microemulsion formulation of bitter orange flower extract and its preparation method. This microemulsion consists of bitter orange flower extract, an emulsifier, a co-emulsifier, an oil phase, a stabilizer, and deionized water, and can be prepared by stirring emulsification or ultrasonic emulsification. However, this microemulsion formulation only targets a single traditional Chinese medicine extract (bitter orange flower extract, with neohesperidin and naringin as the active ingredients), and its applications mainly involve oral addition to pharmaceuticals, food, health products, and cosmetics, without addressing nasal administration or combination with cotton swab carriers.

[0006] Regarding traditional Chinese medicine compositions for the treatment of rhinitis, Chinese patent CN119074826A discloses a pharmaceutical composition for treating rhinitis, which uses water or alcohol extracts of Houttuynia cordata, Chrysanthemum indicum, Lonicera japonica, Centipeda minima, and Senecio scandens as active ingredients, and adds volatile oils such as Xanthium sibiricum oil, Magnolia biondii oil, Mentha haplocalyx oil, Borneol, Angelica dahurica oil, Ligusticum chuanxiong oil, and Notopterygium incisum oil, and adds excipients such as PEG-40 hydrogenated castor oil, anhydrous ethanol, and isopropyl myristate to form an emulsion, which is then mixed with a carbomer gel matrix to prepare a nasal gel. The patent mentions that nasal preparations may include "nasal sticks". However, the technical solution has the following shortcomings: (1) The active part of the composition is a mixture of water extracts of five medicinal materials such as houttuynia cordata and various volatile oils. The system is complex and contains a large amount of water-soluble polymer gel matrix (carbomer 940). It is essentially a semi-solid gel agent, not a microemulsion; (2) Due to the limitation of the polymer network structure, the gel agent has poor fluidity. It is easy to accumulate and spread evenly when applied. Moreover, the gel matrix such as carbomer is easy to form a film after drying, which may block hair follicles or cause discomfort; (3) Its "nasal stick" is essentially a gel application tool. The medicine is not filled into a breakable cotton stick in the form of a microemulsion. The method of administration is fundamentally different from that of this application; (4) The composition contains a large amount of water extract with high water content. It is easy to breed microorganisms and has high requirements for the preservation system. It does not record how to solve the problem of long-term storage stability.

[0007] Furthermore, for extracts of traditional Chinese medicine compound formulas, which contain a variety of components with different properties such as volatile oils, glycosides, flavonoids, alkaloids, and polysaccharides, preparing them into a clear and transparent microemulsion system presents numerous technical challenges and cannot be achieved simply by applying known microemulsion technologies. Especially when microemulsions need to be filled into cotton swabs and meet multiple requirements such as long-term storage stability, rapid saturation of the cotton tip upon application, and a refreshing, non-sticky, and non-irritating effect after application to the nasal mucosa, higher demands are placed on the synergistic matching of the oil phase composition, the type and ratio of emulsifiers, the aqueous phase ratio, and the preservative system. Summary of the Invention

[0008] The core technical problem to be solved by this invention is to overcome the following defects of existing topical rhinitis preparations: (1) Sprays easily irritate the nasal mucosa and trigger a sneezing reflex, causing the liquid to be expelled; (2) Nasal drops are easy to flow back into the throat and have a strong greasy feeling, resulting in poor patient compliance; (3) Existing rhinitis liquid cotton swab products are mostly ordinary emulsions or suspensions with large particle size and poor stability, making it difficult for active ingredients to effectively penetrate the nasal mucosa to exert their effects; (4) Traditional Chinese medicine compound extracts contain a variety of components with different properties, such as volatile oils, glycosides, flavonoids, alkaloids, and polysaccharides, making it difficult to prepare a clear and transparent microemulsion system; (5) When filling microemulsions into breakable cotton swabs, there are problems such as leakage during long-term storage, layering, and uneven wetting of the cotton head; (6) There is currently no rhinitis treatment product that combines a clear and transparent microemulsion form, immediate administration via breakable cotton swabs, a refreshing and non-sticky texture, and is gentle and non-irritating.

[0009] To address the aforementioned problems, this invention provides a microemulsion nasal spray swab and its preparation method. This technical solution precisely combines a compound of ten specific Chinese herbal extracts with a polyoxyethylene 40 hydrogenated castor oil emulsifier to construct a clear and transparent microemulsion system. This system is then filled into a disposable, breakable cotton swab coated with medical absorbent cotton. This not only achieves long-term stable preservation of the microemulsion liquid in the swab but also allows the microemulsion to immediately flow out and saturate the cotton tip when the swab is broken. After application to the nasal cavity, it spreads rapidly and penetrates effectively, providing rapid and long-lasting effects while remaining refreshing, non-sticky, and gentle without irritation.

[0010] Another objective of this invention is to provide a method for preparing the above-mentioned microemulsion nasal spray swabs. By precisely controlling process parameters such as the ratio of oil phase to emulsifier (1:5), stirring rate (300-450 rpm), settling time, and filter cloth specifications, the method ensures that the microemulsion particle size is uniform, the system is clear and transparent, and the stability is reliable. It also enables the filling and sealing of the microemulsion in the swabs.

[0011] Another objective of this invention is to clarify the application of this microemulsion-type nasal solution swab in the preparation of topical products for relieving nasal congestion and dryness symptoms of rhinitis and improving nasal ventilation. Its microemulsion properties and oil-in-water structure are verified through in vitro characterization (Tyndall effect, dilution method, staining method). Its formulation stability is verified through centrifugation stability (10,000 rpm, 30 min) and long-term storage stability (25℃±2℃, 6 months). Its safety is verified through skin irritation test, skin allergy test and acute percutaneous toxicity test. Its onset speed and duration of action are verified through comprehensive sensory evaluation and nasal patency test. Thus, it provides a safe, effective and convenient new option for local nasal administration for rhinitis patients.

[0012] This invention includes the following technical solutions: A microemulsion nasal solution cotton swab, the cotton swab comprising a cotton stalk and a medical absorbent cotton tip covering the end of the cotton stalk, the cotton stalk being filled with microemulsion nasal solution; The microemulsion nasal solution is composed of an oil phase, an aqueous phase, an emulsifier, a preservative and antibacterial agent, and a powder of traditional Chinese medicine extracts. The oil phase is selected from at least two of the following: Xanthium sibiricum oil, Angelica dahurica oil, Asarum heterotropoides oil, Saposhnikovia divaricata oil, Glycyrrhiza uralensis oil, Calendula officinalis oil, Astragalus membranaceus oil, Hibiscus mutabilis leaf oil, Magnolia biondii oil, and Menthol. The emulsifier is polyoxyethylene 40 hydrogenated castor oil; The preservative and antibacterial agent is SC 80; The herbal extract powder is Paris polyphylla extract; The aqueous phase is purified water.

[0013] Furthermore, the oil phase is composed of Xanthium sibiricum oil, Angelica dahurica oil, Asarum heterotropoides oil, Saposhnikovia divaricata oil, Glycyrrhiza uralensis oil, Calendula officinalis oil, Astragalus membranaceus oil, Hibiscus mutabilis leaf oil, Magnolia biondii oil, and menthol.

[0014] Furthermore, based on the mass percentage of each component in the mixed oil phase, the proportions of each component in the oil phase are as follows: Xanthium sibiricum oil 50%–55%, Angelica dahurica oil 1%–2%, Asarum heterotropoides oil 3%–4%, Saposhnikovia divaricata oil 1%–2%, Glycyrrhiza uralensis oil 1%–2%, Calendula officinalis oil 1%–2%, Astragalus membranaceus oil 1%–2%, Hibiscus mutabilis leaf oil 0.05%–0.1%, Magnolia biondii oil 0.05%–0.1%, and Menthol 35%–40%.

[0015] Furthermore, based on the mass percentage of the microemulsion nasal solution, the oil phase is 0.5%–2%, the emulsifier is 5%–10%, the preservative and antibacterial agent is 1%–1.5%, the traditional Chinese medicine extract powder is 0.01%–0.02%, and the remainder is the aqueous phase.

[0016] Furthermore, the preservative and antibacterial agent SC 80 is composed of 1,3-propanediol, octyl glycol, and octyl hydroxamic acid.

[0017] Furthermore, the microemulsion nasal solution is an oil-in-water microemulsion, which appears as a pale yellow, clear, and transparent liquid with a bluish luster. It does not precipitate, become cloudy, or separate into layers when left to stand.

[0018] Furthermore, the cotton swabs are individually packaged for single use.

[0019] This invention also discloses a method for preparing microemulsion nasal spray swabs as described in any of the preceding claims, comprising the following steps: 1) Weigh out each component of the oil phase and mix thoroughly; 2) Filter with nylon filter cloth; 3) Weigh the emulsifier, add it to the filtered oil phase, and stir at room temperature until homogeneous; 4) Weigh the aqueous phase and slowly add it to the mixture obtained in step 3), and continue stirring to mix thoroughly; 5) Weigh out the preservative and antibacterial agent, add it to the mixture obtained in step 4), and continue to stir and mix well; 6) Weigh out the Chinese herbal extract powder, add it to the mixture obtained in step 5), and continue to stir and mix well; 7) After standing at room temperature, filter with nylon filter cloth to obtain microemulsion nasal solution; 8) Fill the obtained microemulsion nasal solution into a cotton stalk wrapped with medical absorbent cotton, seal it, and you will get a microemulsion nasal solution cotton swab.

[0020] Furthermore, in step 1), the stirring rate is 300-450 rpm; in step 2), the nylon filter cloth is 4 layers of 300-350 mesh nylon filter cloth; in step 3), the room temperature is 25℃ and the stirring rate is 300-450 rpm; in step 7), the room temperature is 25℃, the standing time is 1 hour, and the nylon filter cloth is 4 layers of 300-350 mesh nylon filter cloth.

[0021] Furthermore, based on the mass percentage of the microemulsion nasal solution, the oil phase is 0.5%–2%, the emulsifier is 5%–10%, the preservative and antibacterial agent is 1%–1.5%, the traditional Chinese medicine extract powder is 0.01%–0.02%, and the remainder is the aqueous phase.

[0022] The present invention also discloses the application of the above-mentioned microemulsion nasal liquid cotton swabs in the preparation of topical products for relieving nasal congestion and dryness symptoms of rhinitis and improving nasal ventilation.

[0023] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention constructs a clear and transparent microemulsion system by precisely combining a compound of ten traditional Chinese medicine extracts with polyoxyethylene 40 hydrogenated castor oil emulsifier. The ratio of oil phase to emulsifier was determined to be 1:5 through systematic screening (Example 1). At this point, the microemulsion is pale yellow, clear, and transparent with a bluish luster, and is a water-in-oil microemulsion (Example 2). The particle size reaches the nanometer level, which is conducive to the rapid spread and effective penetration of active ingredients on the nasal mucosa, resulting in rapid onset of action (nasal congestion can be relieved immediately upon application) and long-lasting effect (nasal congestion lasts for about 6 minutes, Example 7).

[0024] 2. The polyoxyethylene 40 hydrogenated castor oil used in this invention as an emulsifier, compared to conventional Tween 80, can form a clear and transparent microemulsion (Example 2, Comparative Example 1), and produces a significant Tyndall effect when irradiated with a laser pointer (Example 2). Figure 1 This demonstrates that it has formed a nanoscale dispersion system. The microemulsion has good flowability, no tailing, and is easy to spread, which is beneficial for swab filling and liquid flow from the swab tube, and can effectively stay in the nasal cavity to avoid excessive loss or discomfort.

[0025] 3. This invention, through a systematic comparative design (Example 2), demonstrates the synergistic necessity of a specific combination of Chinese herbal extracts: Comparative Example 2 (lacking Asarum oil and Saposhnikovia oil) showed a significantly reduced effect in relieving nasal congestion and caused slight irritation to the nasal mucosa; Comparative Example 3 (further lacking Calendula oil and Hibiscus leaf oil) showed a further decrease in the effect in relieving nasal congestion to only a slight degree, and a significantly increased irritation to the nasal mucosa. This indicates that Asarum oil, Saposhnikovia oil, Calendula oil, and Hibiscus leaf oil not only have a synergistic effect in clearing nasal passages in this microemulsion system, but also unexpectedly reduce nasal mucosal irritation, and this specific combination is non-obvious.

[0026] 4. The microemulsion nasal solution of the present invention remained clear and transparent, without stratification or precipitation, after being centrifuged at 10,000 rpm for 30 minutes and stored at 25℃±2℃ for 6 months (Example 2), indicating that it has excellent physical stability and long-term storage stability, which is beneficial for industrial production and commercial distribution.

[0027] 5. The pH value of the microemulsion nasal solution of this invention is 5.143±0.008 (Example 2), exhibiting weak acidity, which is compatible with the physiological environment of the nasal cavity. Skin irritation test on New Zealand white rabbits (Example 3), Hartley guinea pig skin allergy test (Example 4), and acute percutaneous toxicity test on SD rats (Example 5) confirmed that this product has no skin irritation, no skin allergic reaction, and is classified as slightly toxic, indicating high safety.

[0028] 6. This invention involves filling a microemulsion nasal solution into a disposable, breakable cotton swab wrapped with medical absorbent cotton. When in use, gently break the swab, and the microemulsion flows through the tube to the cotton tip, where it is applied to the nasal cavity. This cotton swab is individually packaged for single use, ensuring convenience, safety, and hygiene, and avoiding cross-contamination and the risk of reuse.

[0029] 7. The preparation method of this invention has mild process conditions (room temperature operation), controllable operation, and all raw materials are commercially available, showing good industrialization prospects. Comprehensive sensory evaluation (Example 6) showed that all subjects found their nasal cavity comfortable and moist, non-irritating, and breathing smoother after use. 93.55% of subjects were satisfied with the onset speed, 96.77% were satisfied with the duration of effect, and 96.77% reported significant relief from nasal congestion and dryness symptoms, indicating that this product has good application prospects in the field of relieving and treating rhinitis symptoms of nasal congestion and dryness. Attached Figure Description

[0030] Figure 1 This is a comparison diagram of the Tyndall effect of the microemulsion nasal solution of the present invention (the left side is the microemulsion nasal solution, and the right side is the sodium chloride solution). Figure 2 This is an identification diagram of the dilution method for the microemulsion nasal solution of the present invention (left side shows the addition of purified water, right side shows the addition of liquid paraffin); Figure 3 The staining method identification diagram of the microemulsion nasal solution of the present invention (left side shows the solution with methylene blue, right side shows the solution with Sudan red); Figure 4 This is a diagram of the microemulsion nasal solution cotton swab of the present invention. Detailed Implementation

[0031] The following embodiments are intended to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the invention to the scope of the embodiments described.

[0032] The product was prepared from the following raw materials in parts by weight, totaling 5000 parts, of which 50 parts were the oil phase after mixing and filtration. These included: Xanthium sibiricum oil (99% content, Xanthium sibiricum extract, refractive index 1.5285 at 20℃), Angelica dahurica oil (99% content, refractive index 1.4592 at 20℃), Asarum heterotropoides oil (99% content, refractive index 1.4940 at 20℃), Saposhnikovia divaricata oil (99% content, Saposhnikovia divaricata extract, refractive index 1.5199 at 20℃), Glycyrrhiza uralensis oil (99% content, Glycyrrhiza uralensis root extract, refractive index 1.5180 at 20℃), Calendula officinalis oil (99% content, refractive index 1.4758 at 20℃), Astragalus membranaceus oil (99% content, Astragalus membranaceus extract, refractive index 1.4751 at 20℃), and Magnolia biondii oil (99% content, Magnolia biondii flower bud extract, 20℃). The refractive index (1.4798 at ℃) was obtained from Ji'an Zhongxiang Natural Plant Co., Ltd.; the Hibiscus leaf oil (65% content, refractive index 1.453~1.464) was obtained from Jiangxi Hengcheng Natural Fragrance Oil Co., Ltd.; and the Paris polyphylla extract was obtained from Yunnan Baiyao Group Co., Ltd. The preservative and antibacterial agent SC 80 is composed of 1,3-propanediol, octyl glycol, and octanoyl hydroxamic acid, and its trade name is Sensiva. TM SC 80 Multifunctional, sourced from Ashland. In each comparative example, to maintain consistent proportions of emulsifier, aqueous phase, preservative and antibacterial agent, and Paris polyphylla extract, only the composition ratio of the oil phase was changed. In each example, 50 parts of the mixed oil phase were used for final preparation.

[0033] Table 1: Formulation Composition of Examples The specific preparation steps are as follows: 1) Weigh the oil phase and place it in a 300 mL beaker. Use an OS-20Pro mixer to stir and mix at 450 rpm. 2) Use 300-mesh nylon filter cloth for filtration; 3) Weigh the emulsifier into a beaker, add the filtered oil phase, and stir at room temperature using an OS-20Pro mixer at 450 rpm until homogeneous; 4) Then weigh the aqueous phase and slowly add it to 3), continuing to stir and mix thoroughly; 5) Weigh out SC 80 and place it in 4), then continue stirring and mixing until well combined; 6) Then weigh out the Chinese herbal extract powder, add it to 5), and continue to stir and mix well; 7) After standing at room temperature for 1 hour, filter using a 300-mesh nylon filter cloth.

[0034] like Figure 4As shown, the microemulsion nasal spray swab of the present invention includes a cotton rod and a medical degreased cotton tip covering the end of the cotton rod. The cotton rod is filled with microemulsion nasal spray. The swab is individually packaged for single use. When in use, the cotton rod is gently broken, and the microemulsion flows out through the tube to the cotton tip and is applied to the nasal cavity.

[0035] Example 1 Screening of the ratio of oil phase to emulsifier.

[0036] Weigh out 3g of each of the following ratios for oil phase to emulsifier: 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, and 1:8. Stir at 450rpm for 10 minutes using an OS-20Pro mixer, then add 47mL of purified water. Use color and clarity as evaluation indicators to screen for the optimal ratio of oil phase to emulsifier.

[0037] Table 2 shows that when the oil phase to emulsifier mass ratio was 2:1 and 1:1, the solution was milky white and opaque, indicating that a common emulsion had formed, but not yet at the microemulsion level. As the proportion of emulsifier increased, the solution gradually became yellow and slightly transparent. When the oil phase to emulsifier ratio was 1:5, the solution was pale yellow, clear, and transparent with a bluish sheen. Subsequently, as the proportion of emulsifier increased further, the bluish sheen became more pronounced, indicating that the particle size had decreased to the micrometer or even nanometer level, forming a microemulsion or nano-liquid. However, to reduce the amount of emulsifier used, the optimal oil phase to emulsifier ratio was determined to be 1:5.

[0038] Table 2: Screening of oil phase to emulsifier ratio Example 2 Preparation and characterization of microemulsion nasal solution.

[0039] The preparation methods for the examples and comparative examples are as follows: The oil phase components were weighed by weight as follows: 52.5 parts of Xanthium sibiricum oil, 1.75 parts of Angelica dahurica oil, 3.5 parts of Asarum heterotropoides oil, 1.4 parts of Saposhnikovia divaricata oil, 1.05 parts of Glycyrrhiza uralensis oil, 1.75 parts of Calendula officinalis oil, 1.75 parts of Astragalus membranaceus oil, 36.16 parts of Menthol, 0.07 parts of Hibiscus mutabilis leaf oil, and 0.07 parts of Magnolia biondii oil. After mixing thoroughly using an OS-20Pro mixer, the mixture was filtered through four layers of 300-mesh nylon filter cloth and set aside. Weigh 250 parts of emulsifier polyoxyethylene 40 hydrogenated castor oil or Tween 80, add 50 parts of the filtered oil phase, and stir at room temperature (25°C) until homogeneous; weigh 4624.5 parts of purified water, slowly add to the above oil-emulsion mixture and continue stirring until homogeneous; add 75 parts of SC 80, continue stirring until homogeneous, then add 0.5 parts of Paris polyphylla extract, continue stirring until homogeneous, and then let stand at room temperature for 1 hour. Filter using four layers of 300-mesh nylon filter cloth to obtain the final product. The specific preparation method for Comparative Example 2 is as follows: Weigh each component of the oil phase by mass. Weigh 52.5 parts of Xanthium sibiricum oil, 1.75 parts of Angelica dahurica oil, 1.05 parts of Glycyrrhiza uralensis oil, 1.75 parts of Calendula officinalis oil, 1.75 parts of Astragalus membranaceus oil, 36.16 parts of menthol, 0.07 parts of Hibiscus mutabilis leaf oil, and 0.07 parts of Magnolia biondii oil. After mixing thoroughly using an OS-20Pro mixer, filter through four layers of 300-mesh nylon filter cloth and set aside. Weigh 250 parts of emulsifier polyoxyethylene 40 hydrogenated castor oil, add 50 parts of the filtered oil phase, and stir until homogeneous at room temperature (25°C). Weigh 4624.5 parts of purified water (aqueous phase), slowly add it to the above oil-emulsion mixture, and continue stirring until homogeneous. Add 75 parts of SC80, continue stirring until homogeneous, then add 0.5 parts of Paris polyphylla extract, continue stirring until homogeneous, and let stand at room temperature for 1 hour. Filter through four layers of 300-mesh nylon filter cloth to obtain the final product. The specific preparation method for Comparative Example 3 is as follows: Weigh each component of the oil phase by weight. Weigh 52.5 parts of Xanthium sibiricum oil, 1.75 parts of Angelica dahurica oil, 1.05 parts of Glycyrrhiza uralensis oil, 1.75 parts of Astragalus membranaceus oil, 36.16 parts of menthol, and 0.07 parts of Magnolia biondii oil. After mixing thoroughly using an OS-20Pro mixer, filter the mixture through four layers of 300-mesh nylon filter cloth and set aside. Weigh 250 parts of emulsifier polyoxyethylene 40 hydrogenated castor oil, add 50 parts of the filtered oil phase, and stir until homogeneous at room temperature (25°C). Weigh 4624.5 parts of purified water, slowly add it to the above oil-emulsion mixture, and continue stirring until homogeneous. Add 75 parts of SC 80, continue stirring until homogeneous, then add 0.5 parts of Paris polyphylla extract, continue stirring until homogeneous, and let stand at room temperature for 1 hour. Filter the mixture through four layers of 300-mesh nylon filter cloth to obtain the final product. The evaluation results of the examples and comparative examples are based on appearance, nasal congestion relief effect, and nasal mucosal irritation.

[0040] The results showed that the microemulsion nasal solution in the examples, using a specific combination of traditional Chinese medicine extracts and polyoxyethylene 40 hydrogenated castor oil as an emulsifier, was clear and transparent, significantly relieved nasal congestion, and was non-irritating to the nasal mucosa. Compared to the examples, the microemulsion nasal solution in Comparative Example 1, using Tween 80 as an emulsifier, while relieving nasal congestion and being non-irritating to the nasal mucosa, was opaque. Comparative Example 2, with its reduced combination of traditional Chinese medicine extracts containing asarum oil and saposhnikovia oil, significantly reduced its nasal congestion-relieving effect and caused slight irritation to the nasal mucosa. Comparative Example 3, with its reduced combination of traditional Chinese medicine extracts containing asarum oil, saposhnikovia oil, calendula oil, and hibiscus leaf oil, only provided slight nasal congestion relief and caused strong irritation to the nasal mucosa. This indicates that the addition of specific components such as asarum oil, saposhnikovia oil, calendula oil, and hibiscus leaf oil in the examples is beneficial for relieving nasal congestion symptoms and protecting the mucosa. This also indicates that Asarum and Saposhnikovia oil are transdermal penetration enhancers for microemulsion liquid formulations, temporarily altering the nasal mucosal barrier and aiding the penetration of other herbal extracts to improve nasal congestion relief. Their combined use with microemulsion liquid formulations exhibits a synergistic effect. Furthermore, microemulsion liquid formulations possess bioadhesive properties. Preparing oil-soluble herbal extracts into microemulsion liquid formulations not only encapsulates poorly water-soluble and difficult-to-absorb components such as Calendula oil and Hibiscus leaf oil, enabling them to penetrate the nasal mucosal barrier, but also prolongs the residence and release of herbal extracts in the nasal cavity, resulting in a more sustained drug effect. Therefore, the examples provided represent the optimal formulation.

[0041] The microemulsion nasal solution using polyoxyethylene 40 hydrogenated castor oil as an emulsifier was characterized as follows: (1) Appearance: Visually observing the microemulsion nasal solution, the solution is pale yellow, clear and transparent with a bluish luster. No sedimentation, turbidity, or stratification occurs upon standing, indicating that the prepared nasal solution has formed a microemulsion and has good stability. The liquid spreads easily without tailing when poured, indicating that the microemulsion nasal solution has good fluidity, facilitating the filling of cotton swabs and the flow of liquid from the cotton swab tubes. Furthermore, when applied to the nasal cavity, it can effectively remain within the nasal cavity, preventing excessive loss or discomfort.

[0042] (2) Tyndall effect: Microemulsion nasal fluid was irradiated with a laser pointer, while sodium chloride solution was used as a control solution. Figure 1 The results showed that the microemulsion nasal solution produced a clear optical path under laser light, while the sodium chloride solution did not, indicating that the nasal solution had formed a microemulsion.

[0043] (3) Type identification: The type of microemulsion nasal solution was identified by dilution and staining methods. The dilution method is as follows: 1 mL of microemulsion nasal solution was placed in a vial, and 4 mL of purified water and 4 mL of liquid paraffin were added respectively. After shaking, the dispersion was observed. Figure 2The results showed that the microemulsion nasal solution remained homogeneous, stable, and transparent without stratification even after the addition of a large amount of water; however, the addition of a large amount of liquid paraffin resulted in turbidity and stratification, indicating that the microemulsion nasal solution was an oil-in-water emulsion. The staining procedure was as follows: Equal volumes of microemulsion nasal solution were placed in vials, and 1 mL of water-soluble methylene blue and oil-based Sudan Red solutions were added to the microemulsion nasal solution, respectively, and the dispersion was observed. Figure 3 The results showed that methylene blue dye rapidly diffused and colored the microemulsion nasal solution, and the entire system was uniformly blue. In contrast, the added Sudan red dye only appeared red on the surface of the microemulsion nasal solution, further proving that the prepared microemulsion nasal solution was an oil-in-water emulsion.

[0044] (4) Stability: A TGL18M benchtop high-speed refrigerated centrifuge was used to test the centrifugal stability of the microemulsion nasal solution by simulating gravity-induced sedimentation using the centrifugal force generated by high-speed rotation. The specific steps were as follows: The microemulsion nasal solution was placed into 15mL centrifuge tubes and symmetrically placed in the centrifuge. It was centrifuged at 10,000 rpm for 30 min at room temperature (25℃). After centrifugation, the sample was immediately removed and allowed to stand. The results showed that the solution remained unchanged before and after centrifugation, maintaining its transparent state without stratification or precipitation. To further evaluate the stability of the microemulsion nasal solution in practical applications, a 6-month storage stability experiment was conducted. The steps were as follows: The microemulsion nasal solution was sealed and stored at 25℃±2℃ for 6 months. The results showed that the microemulsion nasal solution was stable, clear, and transparent within 6 months, without color change, stratification, or precipitation.

[0045] (5) pH value: The pH value of the microemulsion nasal solution was measured using a PHSJ-5T laboratory pH meter. The results showed that the pH value of the microemulsion nasal solution was 5.143±0.008, which was weakly acidic, indicating that short-term use would hardly irritate the nasal mucosa.

[0046] Example 3 Skin irritation.

[0047] A skin irritation test of a microemulsion nasal solution was conducted using New Zealand white rabbits. The procedure was as follows: Approximately 24 hours before the test, the fur on both sides of the spine of four New Zealand white rabbits was shaved, with each side measuring 3 cm × 3 cm. 0.5 mL of the microemulsion nasal solution (test substance) was applied directly to one side of the skin, covering an area of ​​2.5 cm × 2.5 cm. The other side was treated with the solution as a control. Applications were performed once daily, with results observed one hour after each application, for 14 consecutive days. Skin irritation response scores were calculated according to Table 3, and the average score per animal per day was calculated using the following formula. The intensity of skin irritation was determined according to Table 4. Table 5 shows that, similar to the control group, the microemulsion nasal solution did not cause erythema or edema in the New Zealand white rabbits after repeated skin stimulation, indicating that the microemulsion nasal solution is non-irritating.

[0048] Average score per animal per day = (Σ score of erythema and edema / number of test animals) / 14.

[0049] Table 3: Skin Irritation Response Scores Table 4: Skin Irritation Intensity Grading Table 5: Results of repeated skin irritation tests on New Zealand white rabbits by the test substances Example 4: Skin allergy test.

[0050] A skin allergy test using a localized closed dermal application method was conducted on Hartley guinea pigs using a microemulsion rhinitis solution. The procedure was as follows: Hartley guinea pigs were randomly divided into a microemulsion rhinitis solution group (test substance group), a negative control group, and a positive control group. Twenty-four hours prior to the test, the hair on the left side of the guinea pig's back was shaved, covering an area of ​​4 cm. 2 -6 cm 2 Induction Contact: Approximately 0.2 mL of the test substance was applied to the shaved area on the left side of the guinea pig, covered with two layers of gauze and one layer of cellophane, and then sealed with non-irritating adhesive tape for 6 hours. The negative control group was treated with deionized water and then the same treatment was performed. The positive control group was treated with an induction concentration of 2,4-dinitrochlorobenzene solution and then the same treatment was performed. The same method was repeated on days 7 and 14. Challenge Contact: 14 days after the last induction, approximately 0.2 mL of the test substance was applied to a 2 cm × 2 cm shaved area on the right side of the guinea pig, covered with two layers of gauze and one layer of cellophane, and then sealed with non-irritating adhesive tape for 6 hours. The negative control group was treated with the test substance in the same way during the challenge contact. The positive control group was treated with an challenge concentration of 2,4-dinitrochlorobenzene solution and then the same treatment was performed. Skin reactions were observed 24 hours and 48 hours after the challenge contact. According to the skin reaction scoring in Table 6 and Table 7 of the allergy test, an animal in the test group with a skin reaction score ≥2 was considered to have a positive skin allergy. The sensitization intensity of the microemulsion rhinitis solution was determined according to Table 8. Table 9 shows that at 24h and 48h after challenge exposure, the sensitization rate in the test group was consistent with the negative control group, at 0%, while the sensitization rate in the positive control group was as high as 65% and 40%, respectively. This indicates that no skin allergy was observed in guinea pigs with the microemulsion rhinitis solution.

[0051] Table 6: Skin Reaction Scoring in Allergic Reactions Table 7: Skin Scoring for Allergic Reactions Table 8: Sensitization Intensity Table 9: Results of the skin allergy test on guinea pigs using microemulsion nasal solution Example 5 Acute dermal toxicity test.

[0052] An acute percutaneous toxicity test of a microemulsion nasal solution was conducted using SD rats via a dose-limiting assay. The procedure was as follows: Five male and five female SD rats were administered the microemulsion nasal solution (test substance) percutaneously at a dose of 2180 mg / kg body weight (BW). Approximately 24 hours prior to administration, the fur on the intended toxic area of ​​the animal's back was shaved, ensuring the toxic area covered to at least 10% of the animal's body surface area. On the day of the experiment, the rats were weighed and marked, and the amount of test substance applied was determined based on their body weight. The test substance was evenly applied to the toxic area on the animal's back, then covered with a thin sheet of adhesive tape and secured with non-irritating adhesive tape to prevent licking. The application should be as thin and even as possible. Closed exposure was maintained for 24 hours, and the animals' vital signs were closely monitored for 2-4 hours after administration. After the toxicity period, any remaining test substance was removed. The rats were then observed once daily for 14 days. The signs of poisoning, the appearance and disappearance of symptoms, and the time of death were recorded. Live animals were weighed weekly during the observation period, and surviving animals were weighed at the end of the observation period. After euthanasia, gross anatomical examination was performed. Dermal toxicity was graded according to Table 10. Table 11 shows that the number of deaths after administration of the microemulsion nasal solution was 0, indicating that the acute transdermal median lethal dose (LD50) for female and male SD rats was within acceptable limits. 50 All levels were greater than 2180 mg / kg BW, classifying them as slightly toxic. Gross anatomical examination revealed no abnormalities, and the experimental animals did not exhibit obvious signs of poisoning.

[0053] Table 10: Dermatological Toxicity Classification Table 11: Results of Acute Transdermal Toxicity Tests Example 6 Comprehensive sensory evaluation indicators.

[0054] In this embodiment, the agreement index was evaluated using a 5-point method: 1 point for "strongly disagree," 2 points for "disagree," 3 points for "neutral," 4 points for "agree," and 5 points for "strongly agree." The percentage of people with N ≥ 4 points was counted, and 31 people were tested. Table 12 shows that the microemulsion nasal solution can effectively relieve nasal congestion and dryness symptoms, and does not cause nasal irritation or discomfort during use.

[0055] Table 12: Overall Sensory Evaluation Results Example 7 Nasal decongestion time test.

[0056] To further evaluate the duration of action of the microemulsion nasal solution, a subjective questionnaire was used to evaluate the duration of nasal congestion in 31 participants. The result is the average duration of nasal congestion for all 31 participants. The evaluation criteria were based on a self-controlled pre- and post-treatment approach, with the duration of nasal congestion calculated from the onset of nasal clearing to the disappearance of the nasal clearing effect. Inclusion criteria included healthy males or females aged 18-65 years; participants experiencing nasal congestion and dryness; and participants who were able to cooperate well with the study and maintain a regular lifestyle during the study period. Exclusion criteria: Participants meeting any of the following conditions were excluded. Patients with nasal cavity lesions (inside or outside); those with other non-allergic rhinitis; those with organic diseases such as severe nasal septum deviation, nasal polyps, nasal tumors, or acute sinusitis with fever; those with a recent (within 1 month) history of nasal surgery or trauma; those currently using other nasal medications (such as hormones, decongestants, or antihistamines) or undergoing related treatments; those with skin diseases that may affect the interpretation of test results; those currently experiencing a severe acute allergic attack (such as severe asthma attacks or severe allergic conjunctivitis); pregnant, breastfeeding, or women planning to become pregnant during the testing period; those with severe heart, liver, or kidney dysfunction or severe immunodeficiency; those with mental illness, severe endocrine disorders, or those taking oral contraceptives; those who have participated in drug clinical trials or other trials within the past 30 days, or those who have systematically used medications that may affect test results within the past week; those who have taken oral or topical cosmetic products that may affect test results within the past 2 weeks; and those who cannot cooperate with the test. The administration method is to apply one cotton swab (0.15 mL / swab) to both nasal cavities. The results showed that nasal patency was immediately relieved upon initial application of the nasal ointment, and the nasal patency remained relieved for approximately 6 minutes, indicating that the microemulsion nasal ointment was fast-acting, had a long-lasting effect, and provided good nasal patency relief.

[0057] The above are merely a few preferred embodiments of the present invention, described in a relatively specific and detailed manner, but they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A microemulsion-type nasal spray swab, characterized in that, The cotton swab includes a cotton stalk and a medical absorbent cotton head covering the end of the cotton stalk, and the cotton stalk is filled with microemulsion nasal solution; The microemulsion nasal solution is composed of an oil phase, an aqueous phase, an emulsifier, a preservative and antibacterial agent, and a powder of traditional Chinese medicine extracts. The oil phase is selected from at least two of the following: Xanthium sibiricum oil, Angelica dahurica oil, Asarum heterotropoides oil, Saposhnikovia divaricata oil, Glycyrrhiza uralensis oil, Calendula officinalis oil, Astragalus membranaceus oil, Hibiscus mutabilis leaf oil, Magnolia biondii oil, and Menthol. The emulsifier is polyoxyethylene 40 hydrogenated castor oil; The preservative and antibacterial agent is SC 80; The herbal extract powder is Paris polyphylla extract; The aqueous phase is purified water.

2. The microemulsion nasal spray swab according to claim 1, characterized in that, The oil phase consists of Xanthium sibiricum oil, Angelica dahurica oil, Asarum heterotropoides oil, Saposhnikovia divaricata oil, Glycyrrhiza uralensis oil, Calendula officinalis oil, Astragalus membranaceus oil, Hibiscus mutabilis leaf oil, Magnolia biondii oil, and menthol.

3. The microemulsion nasal spray swab according to claim 2, characterized in that, The proportions of each component in the oil phase, based on their mass percentage in the mixed oil phase, are as follows: Xanthium sibiricum oil 50%~55%, Angelica dahurica oil 1%~2%, Asarum heterotropoides oil 3%~4%, Saposhnikovia divaricata oil 1%~2%, Glycyrrhiza uralensis oil 1%~2%, Calendula officinalis oil 1%~2%, Astragalus membranaceus oil 1%~2%, Hibiscus mutabilis leaf oil 0.05%~0.1%, Magnolia biondii oil 0.05%~0.1%, and Menthol 35%~40%.

4. The microemulsion nasal spray swab according to claim 1, characterized in that, The oil phase comprises 0.5% to 2% of the total mass of the microemulsion nasal solution, the emulsifier comprises 5% to 10%, the preservative and antibacterial agent comprises 1% to 1.5%, the herbal extract powder comprises 0.01% to 0.02%, and the remainder is the aqueous phase.

5. The microemulsion nasal spray swab according to claim 1, characterized in that, The preservative and antibacterial agent SC 80 is composed of 1,3-propanediol, octyl glycol and octyl hydroxamic acid.

6. The microemulsion nasal spray swab according to claim 1, characterized in that, The microemulsion nasal solution is an oil-in-water microemulsion, which appears as a pale yellow, clear, and transparent liquid with a bluish luster. It does not precipitate, become cloudy, or separate when left to stand.

7. The microemulsion nasal spray swab according to claim 1, characterized in that, The cotton swabs are individually packaged for single use.

8. A method for preparing a microemulsion nasal spray swab as described in any one of claims 1-7, characterized in that, Includes the following steps: 1) Weigh out each component of the oil phase and mix thoroughly; 2) Filter with nylon filter cloth; 3) Weigh the emulsifier, add it to the filtered oil phase, and stir at room temperature until homogeneous; 4) Weigh the aqueous phase and slowly add it to the mixture obtained in step 3), and continue stirring to mix thoroughly; 5) Weigh out the preservative and antibacterial agent, add it to the mixture obtained in step 4), and continue to stir and mix well; 6) Weigh out the Chinese herbal extract powder, add it to the mixture obtained in step 5), and continue to stir and mix well; 7) After standing at room temperature, filter with nylon filter cloth to obtain microemulsion nasal solution; 8) Fill the obtained microemulsion nasal solution into a cotton stalk wrapped with medical absorbent cotton, seal it, and you will get a microemulsion nasal solution cotton swab.

9. The preparation method according to claim 8, characterized in that, In step 1), the stirring rate is 300~450 rpm; in step 2), the nylon filter cloth is 4 layers of 300~350 mesh nylon filter cloth; in step 3), the room temperature is 25℃ and the stirring rate is 300~450 rpm; in step 7), the room temperature is 25℃, the standing time is 1 hour, and the nylon filter cloth is 4 layers of 300~350 mesh nylon filter cloth.

10. The preparation method according to claim 8, characterized in that, The oil phase comprises 0.5% to 2% of the total mass of the microemulsion nasal solution, the emulsifier comprises 5% to 10%, the preservative and antibacterial agent comprises 1% to 1.5%, the herbal extract powder comprises 0.01% to 0.02%, and the remainder is the aqueous phase.

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